1. Field
The present invention relates to a technique for inducing epilepsy and a non-human animal model of epilepsy. More particularly, the present invention relates to a method for inducing epilepsy in an animal, a non-human animal model of epilepsy, and a method for manufacturing the same.
2. Description of the Related Art
Epilepsy is a chronic disease to have recurrent seizures which occur as a result of a sudden excessive electrical and synchronized discharge in brain, and is a severe neurological disease accompanied with neurobiological, psychiatric, cognitive, or social impairments.
Epilepsy is one of the most common neurological diseases, affecting approximately 0.5%-1% of the world population. Worldwide, about 45 new epileptic patients per one hundred thousand people are generated every year. In the USA, it is estimated that there are more than 3 million patients with epilepsy, and about 500 new epileptic patients are reported to be generated every day. Further, 70% of cases of epilepsy begin during childhood or adolescence, and in particular, infants are more likely to have epilepsy. The highest incidence and prevalence rates are observed in the first year after the birth of a child, and then drop rapidly. The incidence and prevalence rates rise rapidly again in people over the age of 60, and thus tend to exhibit a U-shaped curve. The prevalence rate of patients who have experienced epileptic seizures in their lives reaches 10-15%.
Epilepsy that fails to respond to anti-epileptic drugs developed until now is called intractable epilepsy, which accounts for approximately 20% cases of epilepsy worldwide.
Malformations of cortical development (MCD) are one of the most common cause of intractable epilepsy. MCDs are a group of disorders characterized by abnormal development of the cerebral cortex due to abnormalities in neuronal migration, differentiation and proliferation, and cause many neurological comorbidities such as developmental delays, mental retardation and cognitive impairments as well as epilepsy. With recent technological advances in brain imaging, such as high-resolution magnetic resonance imaging, etc., diagnosis of malformations of cortical development in patients with intractable epilepsy is rapidly increasing.
Depending on clinical and histopathological features, there are several types of malformations of cortical development. Of them, the most frequent focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC) do not respond to existing anti-epileptic drugs, and thus neurosurgical treatment to remove brain lesions is required for controlling epilepsy.
At present, malformations of cortical development are known to be observed in 50% or more of childhood patients with intractable epilepsy that cannot be controlled with medication and thus should be considered for epilepsy surgery. Malformations of cortical development (sporadic MCD) found in childhood patients may occur in one twin of an identical twin pair, and it is also known that sporadic malformations of cortical development occur without specific family history and external stimulation. Understanding of etiology and pathogenetic mechanisms thereof is insufficient.
Accordingly, there is an urgent need to develop disease model for understanding and studying pathology of malformations of cortical development and epilepsy which cause the same.